Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies

Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs specifically to the tumor cells without damaging healthy organs or tissues. Over the past several decades, efforts have been made to improve drug delivery technologies that target anticancer drugs specifically to tumor cells. It has been known for over four decades that the lymphatics are the first site of metastasis for most solid cancers; however, few efforts have been made to localize chemotherapies to lymphatic tissues. Trials of several systemic targeted drug delivery systems based on nanoparticles containing chemotherapeutic agents (e.g., liposomal doxorubicin) have shown similar antitumor activity but better patient tolerance compared with conventional formulations. Animal studies have demonstrated that nanoparticles made of natural or synthetic polymers and liposomal carriers have higher accumulation in the lymph nodes and surrounding lymphatics compared to conventional intravenous therapies. This combination has the potential to both reduce nonspecific organ toxicities and increase the chemotherapeutic dose to the most likely sites of locoregional cancer metastasis.

[1]  C K Kim,et al.  Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged liposome-entrapped methotrexate to rats. , 1995, Journal of microencapsulation.

[2]  Y. Tokunaga,et al.  Liposomal sustained-release delivery systems for intravenous injection. II. Design of liposome carriers and blood disposition of lipophilic mitomycin C prodrug-bearing liposomes. , 1988, Chemical & pharmaceutical bulletin.

[3]  M. Johnston,et al.  Targeting colloidal particulates to thoracic lymph nodes. , 2006, Lung cancer.

[4]  M. Knopp,et al.  Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[5]  Taryn R. Bagby,et al.  Intralymphatic chemotherapy using a hyaluronan-cisplatin conjugate. , 2008, The Journal of surgical research.

[6]  A. Harris,et al.  A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity , 2005, British Journal of Cancer.

[7]  T. Yamaguchi,et al.  Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer. , 1992, Cancer Research.

[8]  I. Macdonald,et al.  Metastasis: Dissemination and growth of cancer cells in metastatic sites , 2002, Nature Reviews Cancer.

[9]  V. Torchilin,et al.  Targeted delivery of diagnostic agents by surface-modified liposomes , 1994 .

[10]  P. Couvreur,et al.  Lymphatic Targeting of Polymeric Nanoparticles After Intraperitoneal Administration in Rats , 1992, Pharmaceutical Research.

[11]  A. Moossa,et al.  Fluorescent LYVE-1 antibody to image dynamically lymphatic trafficking of cancer cells in vivo. , 2009, The Journal of surgical research.

[12]  R. Liggins,et al.  Paclitaxel loaded poly(L-lactic acid) microspheres for the prevention of intraperitoneal carcinomatosis after a surgical repair and tumor cell spill. , 2000, Biomaterials.

[13]  M. Hashida,et al.  Enhanced lymphatic delivery of mitomycin C conjugated with dextran. , 1984, Cancer research.

[14]  J. Sleeman The lymph node as a bridgehead in the metastatic dissemination of tumors. , 2000, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[15]  Mi-Kyung Lee,et al.  Pharmacokinetics and tissue distribution of methotrexate after intravenous injection of differently charged liposome-entrapped methotrexate to rats , 1994 .

[16]  K. D. Hartman,et al.  Lymphatic absorption and tissue disposition of liposome-entrapped [14C]adriamycin following intraperitoneal administration to rats. , 1981, Cancer research.

[17]  D. Jackson Biology of the lymphatic marker LYVE‐1 and applications in research into lymphatic trafficking and lymphangiogenesis , 2004, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[18]  M. McCarter,et al.  Lymphangiogenesis is pivotal to the trials of a successful cancer metastasis. , 2004, Surgery.

[19]  M. Johnston,et al.  Targeting colloidal particulates to thoracic lymph nodes. Lung Cancer , 2006 .

[20]  P. Kantoff,et al.  Rate of relapse following treatment for localized prostate cancer: a critical analysis of retrospective reports. , 1994, International journal of radiation oncology, biology, physics.

[21]  T. Yamaguchi,et al.  Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice. , 1991, The Tohoku journal of experimental medicine.

[22]  Shin Jung,et al.  Cisplatin-incorporated hyaluronic acid nanoparticles based on ion-complex formation. , 2008, Journal of pharmaceutical sciences.

[23]  Chong-K. Kim,et al.  Lymph node targeting and pharmacokinetics of [3H]methotrexate-encapsulated neutral large unilamellar vesicles and immunoliposomes , 1993 .

[24]  Ruud H. Brakenhoff,et al.  Dissecting the metastatic cascade , 2004, Nature Reviews Cancer.

[25]  Congjian Xu,et al.  Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting , 2006, Cancer Chemotherapy and Pharmacology.

[26]  Lisbeth Illum,et al.  Preparation of Biodegradable, Surface Engineered PLGA Nanospheres with Enhanced Lymphatic Drainage and Lymph Node Uptake , 1997, Pharmaceutical Research.

[27]  Y. Barenholz,et al.  Stability of liposomal doxorubicin formulations: Problems and prospects , 1993, Medicinal research reviews.

[28]  V. Torchilin,et al.  Controlled delivery of Gd-containing liposomes to lymph nodes: surface modification may enhance MRI contrast properties. , 1995, Magnetic resonance imaging.

[29]  C. Nishimura,et al.  Significance of lymphatic invasion on regional lymph node metastasis in early gastric cancer using LYVE-1 immunohistochemical analysis. , 2007, American journal of clinical pathology.

[30]  Magnetic resonance lymphography of profundus lymph nodes with liposomal gadolinium-diethylenetriamine pentaacetic acid. , 2000, Biological & pharmaceutical bulletin.

[31]  G. Storm,et al.  Liposomes to target the lymphatics by subcutaneous administration. , 2001, Advanced drug delivery reviews.

[32]  T. Yotsuyanagi,et al.  Chemotherapy Targeting Regional Lymph Nodes by Gastric Submucosal Injection of Liposomal Adriamycin in Patients with Gastric Carcinoma , 1994, Japanese journal of cancer research : Gann.

[33]  Hisataka Kobayashi,et al.  Lymphatic drainage imaging of breast cancer in mice by micro-magnetic resonance lymphangiography using a nano-size paramagnetic contrast agent. , 2004, Journal of the National Cancer Institute.

[34]  Si-Shen Feng,et al.  Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. , 2004, Current medicinal chemistry.

[35]  S. Sieber,et al.  Carrier activity of sonicated small liposomes containing melphalan to regional lymph nodes of rats. , 1983, Pharmacology.

[36]  B. Fisher Biological and clinical considerations regarding the use of surgery and chemotherapy in the treatment of primary breast cancer , 1977, Cancer.

[37]  J. Sleeman,et al.  The relationship between tumors and the lymphatics: what more is there to know? , 2006, Lymphology.

[38]  S. Sieber,et al.  Enhanced lymph node uptake of melphalan following liposomal entrapment and effects on lymph node metastasis in rats. , 1982, Cancer treatment reports.